Nitisinone, although unapproved for use in
alkaptonuria (AKU), is currently the only
homogentisic acid lowering
therapy with a potential to modify
disease progression in AKU. Therefore, safe use of
nitisinone off-label requires identifying and managing
tyrosine keratopathy. A 22-year-old male with AKU commenced 2 mg daily
nitisinone after full assessment. He was issued an alert card explaining potential ocular symptoms such as red eye, tearing, ocular
pain and
visual impairment and how to manage them. On his first and second annual follow-up visits to the National
Alkaptonuria Centre (NAC), there was no corneal keratopathy on
slit lamp examination. On his third follow-up annual visit to the NAC, he was found to have typical dendritiform corneal keratopathy in both eyes which was asymptomatic.
Nitisinone was suspended until a repeat
slit lamp examination, 2 weeks later, confirmed that the keratopathy had resolved. He recommenced
nitisinone 2 mg daily with a stricter
low protein diet. On his fourth annual follow-up visit to the NAC, a routine
slit lamp examination showed mild corneal keratopathy in the left eye. This is despite him reporting no ocular symptoms. This case highlights the fact that corneal keratopathy can occur without symptoms and any monitoring plan with
off-label use of
nitisinone in AKU will need to take this possibility into account. This is also the first time that typical corneal keratopathy has been described with the use of low dose
nitisinone in AKU without symptoms.